Vitamin B12 Deficiency and Hyperhomocysteinemia in Outpatients with Stroke or Transient Ischemic Attack: a cohort study at an academic medical centre

Objective We sought to assess the current magnitude of the opportunity for secondary stroke prevention with B vitamins. Design A cohort study. Setting The Urgent TIA (Transient Ischaemic Attack) Clinic at an academic medical centre. Main outcome measures We assessed the prevalence of biochemical vitamin B 12 deficiency (B 12 Def, serum B 12 \u3c156 pmol/L), hyperhomocysteinaemia (HHcy; plasma total homocysteine [tHcy] \u3e14 μmol/L) and metabolic B 12 deficiency (MetB 12 Def, serum B 12 \u3c258 pmol/L and HHcy) between 2002 and 2017, by age group and by stroke subtype. Results Data were available in 4055 patients. B 12 Def was present in 8.2% of patients overall; it declined from 10.9% of patients referred before 2009 to 5.4% thereafter (p=0.0001). MetB 12 Def was present in 10.6% of patients, and HHcy was present in 19.1% of patients. Among the patients aged ≥80 years, MetB 12 Def was present in 18.1% and HHcy in 35%. Among the 3410 patients whose stroke subtype was determined, HHcy was present in 18.4% of patients: 23.3% of large artery atherosclerosis, 18.1% of cardioembolic, 16.3% of small vessel disease, 10.8% of other unusual aetiologies and 13.6% of undetermined subtypes (p=0.0001). Conclusions Despite a decline in our referral area since 2009, B 12 Def, MetB 12 Def and HHcy remain common in patients with stroke/TIA. Because these conditions are easily treated and have serious consequences, all patients with stroke/TIA should have their serum B 12 and tHcy measured

Spinal arteriovenous shunts presenting as intracranial subarachnoid haemorrhage

Item does not contain fulltextBACKGROUND: In approximately 5% of patients with intracranial subarachnoid haemorrhage (SAH), the cause is another than a ruptured aneurysm or perimesencephalic haemorrhage. One of these causes is a spinal arteriovenous shunt (SAVS). The aim of this study was to investigate the characteristics of patients with SAVS who present with intracranial SAH without symptoms and signs suggesting a spinal cause. METHODS: We systematically reviewed the literature and searched the SAH database of the University Medical Center Utrecht, The Netherlands, for patients with SAVS presenting with intracranial SAH and studied the characteristics of patients with SAVS whose clinical presentation mimicked intracranial SAH caused by rupture of a saccular aneurysm. RESULTS: Thirty-five patients were identified after a review of the literature. In our SAH database, comprising 2142 patients included in the period 1985-2004, we found one patient (0.05%, 95 % CI 0.006- 0.3%). SAH due to SAVS occurred at any age (4-72 years). The SAVS was located at the craniocervical junction in 14 patients, at the cervical level in 11, and at the thoracolumbar level in the remaining 11 patients. The majority of patients (n = 26, 72%) had no disabling deficits at discharge or follow-up. CONCLUSION: Rupture of a SAVS presenting as intracranial SAH is rare and can occur at any age. The SAVS can be located not only at the craniocervical junction or cervical level but also in the thoracolumbar region. Most patients with SAVS presenting as intracranial SAH have a good recovery

Caregiving concerns and clinical characteristics across neurodegenerative and cerebrovascular disorders in the Ontario neurodegenerative disease research initiative

Objectives: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit\u27s Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders?. Methods/Design: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer\u27s disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson\u27s disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living (ADL)). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI. We then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery. Results: We found three components in the ZBI. The first was “overall burden” and was (1) strongly related to increased neuropsychiatric symptoms (NPI severity r = 0.586, NPI distress r = 0.587) and decreased independence in ADL (instrumental ADLs r = −0.566, basic ADLs r = −0.43), (2) moderately related to cognition (MoCA r = −0.268), and (3) showed little-to-no differences between disorders. The second and third components together showed four types of caregiving concerns: current care of the person with the neurodegenerative disease, future care of the person with the neurodegenerative disease, personal concerns of study partners, and social concerns of study partners. Conclusions: Our results suggest that the experience of caregiving in neurodegenerative and cerebrovascular diseases is individualized and is not defined by diagnostic categories. Our findings highlight the importance of targeting ADL and neuropsychiatric symptoms with caregiver-personalized solutions

Targeted copy number variant identification across the neurodegenerative disease spectrum

Background: Although genetic factors are known to contribute to neurodegenerative disease susceptibility, there remains a large amount of heritability unaccounted for across the diagnoses. Copy number variants (CNVs) contribute to these phenotypes, but their presence and influence on disease state remains relatively understudied. Methods: Here, we applied a depth of coverage approach to detect CNVs in 80 genes previously associated with neurodegenerative disease within participants of the Ontario Neurodegenerative Disease Research Initiative (n = 519). Results: In total, we identified and validated four CNVs in the cohort, including: (1) a heterozygous deletion of exon 5 in OPTN in an Alzheimer\u27s disease participant; (2) a duplication of exons 1–5 in PARK7 in an amyotrophic lateral sclerosis participant; (3) a duplication of \u3e3 Mb, which encompassed ABCC6, in a cerebrovascular disease (CVD) participant; and (4) a duplication of exons 7–11 in SAMHD1 in a mild cognitive impairment participant. We also identified 43 additional CNVs that may be candidates for future replication studies. Conclusion: The identification of the CNVs suggests a portion of the apparent missing heritability of the phenotypes may be due to these structural variants, and their assessment is imperative for a thorough understanding of the genetic spectrum of neurodegeneration

Task-Selective Memory Effects for Successfully Implemented Encoding Strategies

Previous behavioral evidence suggests that instructed strategy use benefits associative memory formation in paired associate tasks. Two such effective encoding strategies–visual imagery and sentence generation–facilitate memory through the production of different types of mediators (e.g., mental images and sentences). Neuroimaging evidence suggests that regions of the brain support memory reflecting the mental operations engaged at the time of study. That work, however, has not taken into account self-reported encoding task success (i.e., whether participants successfully generated a mediator). It is unknown, therefore, whether task-selective memory effects specific to each strategy might be found when encoding strategies are successfully implemented. In this experiment, participants studied pairs of abstract nouns under either visual imagery or sentence generation encoding instructions. At the time of study, participants reported their success at generating a mediator. Outside of the scanner, participants further reported the quality of the generated mediator (e.g., images, sentences) for each word pair. We observed task-selective memory effects for visual imagery in the left middle occipital gyrus, the left precuneus, and the lingual gyrus. No such task-selective effects were observed for sentence generation. Intriguingly, activity at the time of study in the left precuneus was modulated by the self-reported quality (vividness) of the generated mental images with greater activity for trials given higher ratings of quality. These data suggest that regions of the brain support memory in accord with the encoding operations engaged at the time of study

Added value of multiphase CTA imaging for thrombus perviousness assessment

Purpose: Thrombus perviousness has been associated with favorable functional outcome in acute ischemic stroke (AIS) patients. Measuring thrombus perviousness on CTA may be suboptimal due to potential delay in contrast agent arrival in occluded arteries at the moment of imaging. Dynamic sequences acquired over time can potentially overcome this issue. We investigate if dynamic CTA has added value in assessing thrombus perviousness. Methods: Prospectively collected image data of AIS patients with proven occlusion of the anterior or posterior circulation with thin-slice multi-phase CTA (MCTA) and non-contrast CT were co-registered (n = 221). Thrombus attenuation increase (TAI; a perviousness measure) was measured for the arterial, venous, and delayed phase of the MCTA and time-invariant CTAs (TiCTA). Associations with favorable clinical outcome (90-day mRS ≤ 2) were assessed using univariate and multivariable regressions and calculating areas under receiver operating curves (AUC). Results: TAI determined from the arterial phase CTA was superior in the association with favorable outcome with OR = 1.21 per 10 HU increase (95%CI 1.04–1.41, AUC 0.62, p = 0.014) compared to any other phase (venous 1.14(95%CI 1.01–1.30, AUC 0.58, p = 0.033), delayed 1.046(95%CI 0.919–1.19, AUC 0.53, p = 0.50)), and TiCTA (1.15(95%CI 1.02–1.30, AUC 0.60, p = 0.022). In the multivariable model, only TAI on arterial phase was

Statistical Epistasis and Functional Brain Imaging Support a Role of Voltage-Gated Potassium Channels in Human Memory

Despite the current progress in high-throughput, dense genome scans, a major portion of complex traits' heritability still remains unexplained, a phenomenon commonly termed “missing heritability.” The negligence of analytical approaches accounting for gene-gene interaction effects, such as statistical epistasis, is probably central to this phenomenon. Here we performed a comprehensive two-way SNP interaction analysis of human episodic memory, which is a heritable complex trait, and focused on 120 genes known to show differential, memory-related expression patterns in rat hippocampus. Functional magnetic resonance imaging was also used to capture genotype-dependent differences in memory-related brain activity. A significant, episodic memory-related interaction between two markers located in potassium channel genes (KCNB2 and KCNH5) was observed (Pnominal combined = 0.000001). The epistatic interaction was robust, as it was significant in a screening (Pnominal = 0.0000012) and in a replication sample (Pnominal = 0.01). Finally, we found genotype-dependent activity differences in the parahippocampal gyrus (Pnominal = 0.001) supporting the behavioral genetics finding. Our results demonstrate the importance of analytical approaches that go beyond single marker statistics of complex traits

Visual Personal Familiarity in Amnestic Mild Cognitive Impairment

BACKGROUND: Patients with amnestic mild cognitive impairment are at high risk for developing Alzheimer's disease. Besides episodic memory dysfunction they show deficits in accessing contextual knowledge that further specifies a general concept or helps to identify an object or a person. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging, we investigated the neural networks associated with the perception of personal familiar faces and places in patients with amnestic mild cognitive impairment and healthy control subjects. Irrespective of stimulus type, patients compared to control subjects showed lower activity in right prefrontal brain regions when perceiving personally familiar versus unfamiliar faces and places. Both groups did not show different neural activity when perceiving faces or places irrespective of familiarity. CONCLUSIONS/SIGNIFICANCE: Our data highlight changes in a frontal cortical network associated with knowledge-based personal familiarity among patients with amnestic mild cognitive impairment. These changes could contribute to deficits in social cognition and may reduce the patients' ability to transition from basic to complex situations and tasks

Thrombolysis Administration After Minor Ischemic Stroke Not Associated with Subsequent Dementia Incidence

Background: Thrombolysis (tPA) administered within 4.5 hours of ischemic stroke is the current standard of care for hyperacute stroke management. Utilization of tPA increased after the implementation of integrated stroke care in Ontario, Canada. We have recently shown that tPA administered within 4.5 hours of stroke onset is associated with reduced risk of dementia incidence. Given the wide spectrum of stroke severities, we investigated whether this clinical benefit persisted among those diagnosed with minor stroke. Methods: We included all minor ischemic stroke patients (NIHSS\u3c = 5) from July 1, 2003 to March 31, 2013 in the Ontario Stroke Registry (OSR) who were free of dementia at stroke onset. Patients were followed after stroke for dementia incidence at 1 year and 4 years. Dementia diagnosis was obtained using a validated algorithm from administrative databases. Cox regression, with death adjusted as competing risk and hospitals as random effects, modelled thrombolysis administration following stroke and dementia incidence, while adjusting for demographic and clinical characteristics. Data was analyzed at the Institute for Clinical Evaluative Sciences. Results: A total of 9,633 stroke patients were included in the analysis. Thrombolysis reduced the risk of dementia incidence by 12% at 1 year post-stroke [cause-specific HR = 0.88 (95% CI:0.57–1.36) and by 2% at 4 years post-stroke [cause-specific HR = 0.98 (95% CI:0.66–1.47). Conclusions: Among patients with NIHSS\u3c = 5, administration of thrombolytic therapy was not associated with reduced risk of dementia incidence 1 year and 4 years following minor stroke onset